Primary choriocarcinoma of the urinary bladder

A 72-year-old woman with asymptomatic macrohematuria was referred to our hospital. Cystoscopy revealed a 7 cm sessile tumor on the left lateral wall of the bladder. Subsequently an intravenous pyelography revealed left hydronephrosis. We performed transurethral biopsy and resection of the bladder tumor under the diagnosis of ordinary malignant bladder tumor. Histopathologically, the lesion was shown to be an undiffentiated urothelial carcinoma, G3, > or = pT2, containing syncytiotrophoblastic giant cells. The level of serum human chorionic gonadotropin-beta (hCG-beta) level was slightly elevated (0.3 ng/ml; normal value: < 0.1). Because a further examination revealed an invasion into the surrounding fat tissue of the bladder and left ureter, a total cystohysterectomy with an ileal conduit were performed. The final histopathological classification was choriocarcinoma of the urinary bladder, pT3a, pN1, pMx. An adjuvant combination chemotherapy was carried out using methotrexate, vinblastine, adriamycin and cisplatin (MVAC). After two courses of chemotherapy, the serum hCG-beta levels returned to normal. Eleven months postoperatively, however, there was evidence of multiple lung metastases. The patient died 12 months after the surgery as a result of complications caused by widespread metastases.     

Superior vena cava syndrome caused by supraclavicular lymph node metastasis of renal cell carcinoma

A 65-year-old woman presented with gross hematuria in February 1997. Left renal tumor was revealed and radical nephrectomy was performed. Pathological examination revealed papillary renal cell carcinoma, pT3aN1M1 (ipsilateral adrenal gland). Interferon-α was administered for 1 year. Two years after the nephrectomy, metastasis to the left supraclavicular lymph node appeared. Seven years after the nephrectomy, the metastatic tumor invaded the brachiocephalic vein and extended to the superior vena cava (SVC), compatible with SVC syndrome. Although interferon-α and external-beam radiotherapy was performed, she died in February 2005. Autopsy revealed a left supraclavicular lymph node metastasis invading the thyroid gland, mediastinum, and brachiocephalic vein. The tumor thrombus descended via the SVC into the right atrium. The right lung artery was obstructed by tumor thrombus. There were no visceral metastases and no local recurrence.     

Lack of association between CpG island methylator phenotype in human gastric cancers and methylation in their background non-cancerous gastric mucosae

The presence of high levels of aberrant DNA methylation in gastric mucosae correlates with risk of gastric cancer. Some gastric cancers are known to have methylation of multiple CpG islands (CGI), which is referred to as the CGI methylator phenotype (CIMP). In the present study, we aimed to clarify the possible association between the CIMP in cancers and high methylation levels in their background mucosae by accurate quantitative methylation analysis of 14 carefully selected promoter CGI. Methylation levels were measured in 66 cancers and their background mucosae, along with 19 normal mucosae of healthy volunteers. Methylation in cancers was classified as absent (methylation level = 0%) or positive. The number of methylated CGI in a cancer showed a continuous distribution, and cancers were classified as CIMP high (21 cases), CIMP low (30 cases), or CIMP negative (15 cases). CIMP-high gastric cancer patients had significantly better survival rates than CIMP-negative patients. Of the Epstein–Barr virus-positive gastric cancers studied, eight out of nine presented as CIMP high. Methylation in background mucosae showed a unimodal distribution, and was assessed by their degree. The gastric mucosae of cancer patients showed higher levels than normal gastric mucosae of healthy volunteers. Finally, the CIMP-high, CIMP-low, and CIMP-negative statuses in cancers were not associated with methylation levels of individual genes and their means in the background mucosae. These showed that the CIMP statuses in gastric cancers had no association with methylation levels in the background gastric mucosae. ( Cancer Sci 2007; 98: 1853–1861)     

Concomitant activation of AKT with extracellular-regulated kinase 1/2 occurs independently of PTEN or PIK3CA mutations in endometrial cancer and may be associated with favorable prognosiss

Deregulated signaling via the phosphatidylinositol 3-kinase (PI3K) pathway is common in many types of cancer, but its clinicopathological significance in endometrial cancer remains unclear. In the present study, we examined the status of the PI3K signaling pathway, especially in relation to PTEN and PIK3CA status, in endometrioid-type endometrial cancer. The immunohistochemical analysis revealed a high level of phosphorylated (p)-AKT expression, which is a hallmark of activated PI3K signaling, in approximately 60% of endometrial cancers. There was no correlation between p-AKT expression and clinicopathological characteristics, such as International Federation of Gynecology and Obstetrics stage, tumor grade, and myometrial invasion. Unexpectedly, a high level of p-AKT expression occurred independently of the presence of PTEN or PIK3CA mutations. Furthermore, p-AKT expression did not correlate with the expression of potential downstream targets, including p-mTOR and p-FOXO1/3a. In turn, p-AKT expression was strongly associated with extracellular-regulated kinase 1/2 expression ( P =  0.0031), which is representative of the activated RAS–MAP kinase pathway. Kaplan–Meier analysis suggested that low p-AKT expression was associated with low rates of relapse-free survival, although the difference was not statistically significant, indicating that AKT activation does not confer worse prognosis. The present study demonstrates the presence of complex signaling pathways that might mask the conventional tumorigenic PTEN–PI3K–AKT–mTOR pathway, and strongly suggests a close association between the extracellular-regulated kinase and PI3K pathways in this tumor type. ( Cancer Sci 2007; 98: 1881–1888)     

Efficacy of preoperative radiotherapy to portal vein tumor thrombus in the main trunk or first branch in patients with hepatocellular carcinoma

Background The prognosis of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) in the main trunk or the first branch is very poor. Methods Radiotherapy (RT) to PVTT was followed by hepatectomy within 2 weeks. The dose used was 30–36 Gy, in 10–12 fractions, for 15–20 days. The efficacy of preoperative RT to PVTT in the main trunk or first branch was evaluated by comparing results in patients who underwent hepatectomy (group R; n = 15) with preoperative RT and those without preoperative RT (group N; n = 28). Results The 1-, 3-, and 5-year survival rates in group R were 86.2%, 43.5%, and 34.8%, respectively, while these values in group N were 39.0%, 13.1%, and 13.1%, respectively. The survival curve of group R was significantly better than that of group N (P = 0.0359). In group R, five (83.3%) of six patients whose tumor thrombus was completely necrosed (based on pathological examination) and whose follow-up period was over 2 years survived for more than 2 years. Female sex (P = 0.0066), multiple tumors (P = 0.0369), and absence of preoperative RT (P = 0.0359) were ranked as significant factors for a poor prognosis by univariate analysis. Multivariate analysis revealed absence of preoperative RT and female sex to be significant factors for a poor prognosis. Conclusion Preoperative RT to PVTT in the main trunk or first branch improved the prognosis of patients with HCC with PVTT, and could be a promising new modality in the treatment of these patients.     

Association of <Emphasis Type="Italic">TP53</Emphasis>codon 72 polymorphism and the outcome of adjuvant therapy in breast cancer patients

Introduction  

Single-nucleotide polymorphisms (SNPs) in codon 72 of the TP53 (also known as p53) gene (rs1042522) and in the promoter region of the MDM2 gene (SNP309; rs2279744) have been suggested to play roles in many cancers. We investigated whether these SNPs were associated with patient outcome and the effect of adjuvant systemic therapy.     

Fluorescence-guided resection of metastatic brain tumors using a 5-aminolevulinic acid-induced protoporphyrin IX: pathological study

We performed a pathological study to identify the locus of production of protoporphyrin IX (PPIX) in human metastatic brain tumors. Patients with metastatic brain tumors (n = 11) received 1 g of 5-aminolevulinic acid (5-ALA) perorally 2 h before undergoing surgery. The target region was exposed to laser light with a peak wavelength of 405 ± 1 nm and an output of 40 mW. Tissue samples from the tumor bulk and surrounding areas were examined by histological and fluorescence methods. Of the 11 tumors, 9 manifested PPIX fluorescence in the tumor bulk and peritumoral brain tissue. Our findings indicate that PPIX fluorescence can be observed in peritumoral edematous areas that are free of neoplastic cells, because PPIX produced by neoplastic cells leaks into the surrounding edematous area.     

Reproducibility of the abdominal and chest wall position by voluntary breath-hold technique using a laser-based monitoring and visual feedback system

PURPOSE: The voluntary breath-hold (BH) technique is a simple method to control the respiration-related motion of a tumor during irradiation. However, the abdominal and chest wall position may not be accurately reproduced using the BH technique. The purpose of this study was to examine whether visual feedback can reduce the fluctuation in wall motion during BH using a new respiratory monitoring device. METHODS AND MATERIALS: We developed a laser-based BH monitoring and visual feedback system. For this study, five healthy volunteers were enrolled. The volunteers, practicing abdominal breathing, performed shallow end-expiration BH (SEBH), shallow end-inspiration BH (SIBH), and deep end-inspiration BH (DIBH) with or without visual feedback. The abdominal and chest wall positions were measured at 80-ms intervals during BHs. RESULTS: The fluctuation in the chest wall position was smaller than that of the abdominal wall position. The reproducibility of the wall position was improved by visual feedback. With a monitoring device, visual feedback reduced the mean deviation of the abdominal wall from 2.1 +/- 1.3 mm to 1.5 +/- 0.5 mm, 2.5 +/- 1.9 mm to 1.1 +/- 0.4 mm, and 6.6 +/- 2.4 mm to 2.6 +/- 1.4 mm in SEBH, SIBH, and DIBH, respectively. CONCLUSIONS: Volunteers can perform the BH maneuver in a highly reproducible fashion when informed about the position of the wall, although in the case of DIBH, the deviation in the wall position remained substantial.     

Treatment strategy for the type IV gastric cancer--from the standpoint of the surgery

From the standpoint of the surgery, the treatment strategy for the type IV gastric cancer (GC) was studied. Recently, the resected rate of type IV GC has been increasing, though the number of operated GC patients is decreasing. The five-year survival rate was about 20% in all and around 30% in the curatively resected pts. As a result of examination of our pts with type 4 GC, multimodality therapy including neoadjuvant chemotherapy and extended surgery is recommended for pts with P 0/CY 0 or P 0/CY 1 but without other remaining GC lesions. Palliative gastrectomy and postoperative chemotherapy are recommended if performed safely to prevent such symptoms in spite of unresectable metastasis for pts with urgent symptoms such as bleeding, stricture, pain or malnutrition. For pts with P 2/P 3 but without passage disturbance, intensive chemotherapy is selected. But the propriety for selection of reduction surgery for pts with P 2/P 3 is controversial. The results of the prospective randomized controlled study of reduction surgery in non-curative advanced gastric cancer by the Gastric Cancer Surgical Study Group in Japan Clinical Oncology Group (JCOG) are expected.